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Biomedical subjects

T B Lin

Publications and source records attributed to T B Lin.

10 recordsLinked to original sources

Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K(+)-channel Kv2.1.

The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3C upon toxin binding is presented as a possible explanation for the observed shift in hanatoxin binding-induced gating.

Animals↗

Effect of electroacupuncture on blood pressure and adrenal nerve activity in anesthetized rats.

The neural mechanism underlying the effect of electroacupuncture (Ea) on arterial blood pressure (BP) and adrenal nerve activity (ANA) was investigated in anesthetized rats. Tsusanli (St-36) and Hoku (Li-4) were tested with combinations of two different frequencies (3 and 30 Hz) with various stimulation intensities of Ea. At Tsusanli, no effect was found, while at Hoku, an elevation of BP in parallel with ANA was elicited during Ea when the intensity was 5xT or higher. The pattern of the pressor response caused by the low frequency Ea (LFEa, 3 Hz) was a tonic one, while a phasic one was induced by the high frequency Ea (HFEa, 30 Hz). When both Hoku were simultaneously stimulated with the same frequency, the latency to reach the maximal effect was shortened. However, when two different frequencies were used instead, a response characterized by a combination of both phasic and tonic effect was obtained. In bilateral Ea with idential frequency but different onset time, the pressor effect elicited by the latter Ea showed no further increase during the stimulation period, however, when different frequencies were employed, each Ea elicited its own effect independently. The pressor effect elicited by Ea was abolished by regitine but not affected by adrenalectomy. It is concluded that a LFEa and a HFEa at Hoku with appropriate stimulation parameters can increase BP which is mainly due to potentiation of the sympathetic vasoconstrictor tone but via different central mechanisms.

Adrenal Glands↗

Neural mechanisms of impaired micturition reflex in rats with acute partial bladder outlet obstruction.

To determine the contribution of neural elements to micturition, we evaluated, in intact rats, the cystometrogram, pelvic afferent nervous activity, pelvic efferent nervous activity and external urethral sphincter-electromyogram activity in the normal and acute partial bladder outlet obstruction states. In the normal state, in response to saline filling, mechanoreceptor-dependent pelvic afferent nervous activity gradually activated and finally triggered a voiding reflex, including four phases of detrusor contractions. Phase 1 was characterized by an initial rising intravesical pressure, Phase 2 was characterized by a series of high-frequency oscillations in intravesical pressure, Phase 3 contraction was characterized by a rebound intravesical pressure and Phase 4 contraction was characterized by a rapid fall in intravesical pressure. In the acute partial bladder outlet obstruction state, Phase 1 contraction rose and high-frequency oscillations fell in Phase 2. This voiding dysfunction is ascribed to the bursting extraurethral sphincter activity being converted to tonic extraurethral sphincter activity. In summary, the suppressed high-frequency oscillations in Phase 2 of the detrusor muscle contraction could be detrimental to efficient voidings in the acute partial bladder outlet obstructed rat.

Acute Disease↗

Contralaterally induced dorsal root reflex shares common final pathway with ipsilaterally elicited ones in Wistar rats.

The dorsal root reflex (DRR) in single fibers, recorded in the severed L5 dorsal root central stump, initiated by sciatic nerve (SN) stimulation (St), was studied in anesthetized rats. Both ipsi- and contralateral Sts elicited DRR, with central delays of 4.6 +/- 0.3 (n = 10) and 27.3 +/- 2.5 (n = 5) ms, respectively. Ipsilaterally induced DRRs showed repetitive firing (mean = 3 +/- 0.5 spikes, n = 5), while contralaterally induced ones were abolished after spinalization (T13). When the time interval between two ipsilateral suprathreshold Sts was less than 12 +/- 2.4 ms (n = 12), the second DRR was abolished. On the other hand, when it between two ipsilateral subthreshold Sts was less than 4.8 +/- 0.3 ms (n = 7), DRR was activated. Contralaterally induced DRR also showed temporal inhibition and facilitation with time intervals similar to that in ipsilateral cases. Furthermore, when the latency between a contralaterally and a ipsilaterally induced DRR was less than 10.8 +/- 1.8 ms (n = 5), the later DRR was blocked by the former, and vice versa. Facilitation can be also shown by a contralateral and a ipsilateral subthreshold St. These results suggested that contralaterally induced DRRs may share part of final common pathway with ipsilaterally induced ones.

Animals↗

Nicotine-induced hyperlocomotion is not modified by the estrous cycle, ovariectomy and estradiol replacement at physiological level.

The present study was designed to investigate whether nicotine's effect on locomotion might be modulated by the ovarian hormone at physiological level. Rats at normal cycling of estrus and diestrus were selected for the comparison of nicotine-induced hyperlocomotion based on the document that the release of striatal dopamine was greatest at the estrous phase. Ovariectomized rats primed with or without estrogen at physiological level were also selected for comparison. Increase in spontaneous locomotion by nicotine was statistically significant at the doses of 0.15 and 0.3 mg/kg (p < 0.001). The stimulating effect of nicotine led the locomotor response to almost the same magnitude in all hormonal groups studied. Nicotine-induced hyperlocomotion appeared to be mediated by central nicotinic receptor because it was blocked by mecamylamine (0.5 and 1.0 mg/kg, i.p.). Also it was blocked by haloperidol (0.04 and 0.08 mg/kg, i.p.) indicating the involvement of dopaminergic neurotransmission. These effects were similar in all groups regardless of the estrous cycle or ovariectomy. The observed data provided behavioral evidence to suggest that the effect of nicotine on locomotion-related dopaminergic neurons might not be modified by the physiological action of estrogen.

Animals↗

Which afferents induce and transmit dorsal root reflex in rats?

The dorsal root reflex (DRR) in single fibers, recorded in the severed L5 dorsal root central stump, initiated spontaneously or by electric stimulation (St) of sciatic nerve, was studied in anesthetized rats. The excitation of group II afferents were the major inputs to induce DRRs which were transmitted mainly in fibers with conduction velocity below 20 m/s, and its central delay was 3-5 ms. The firing frequency of both spontaneous and evoked DRRs were increased two to four times after spinalization (T13). These results suggested that the DRR may play an important role in the modulation of sensory afferent inputs regulated by supraspinal structures.

Afferent Pathways↗

Low and high frequency electroacupuncture at Hoku elicits a distinct mechanism to activate sympathetic nervous system in anesthetized rats.

To address the effect of electroacupuncture (Ea) on autonomic nerve activity, the responses of rhythmic micturition contraction (RMC), urine excretion (UE), blood pressure (BP), renal sympathetic nerve activity (RNA) and pelvic parasympathetic nerve activity (PNA) to Ea were investigated in urethane-anesthetized rats. The acupoint Hoku (Li-4) was tested with two different stimulation frequencies (2 Hz and 20 Hz). Elongation of the RMC cycle and an increase in UE associated with the elevation of BP and RNA was elicited during Ea at Hoku. However, the pressor response induced by low frequency Ea (LFEa) was different from that by high frequency Ea (HFEa), i.e. a tonic effect was elicited by LFEa, while a phasic one was induced by HFEa. These results imply that: (1) Ea at Hoku may selectively activate the sympathetic, but not the parasympathetic nervous system, (2) Ea at Hoku with a different stimulation frequency may elicit a distinct mechanism to activate the sympathetic nervous system and (3) Ea at Hoku may ameliorate the hyperactive bladder in clinical therapy.

Acupuncture Points↗

Can antidromic stimulation of rat muscle afferents modulate the sensitivity of muscle spindles?

The sensitivity of muscle spindles in gastrocnemius-soleus (GS) muscles following dorsal root (DR) antidromic stimulation (ASt) was investigated in anesthetized rats, in which the hindleg was totally denervated except the GS muscle, ventral roots from L3 to S1 and DRs from L4 to L6, which were severed after laminectomy. The peripheral end of a teased DR filament with single unit tonic discharges from a constantly stretched muscle spindle were recorded and antidromically stimulated after identification. In response to ASt with various frequencies, two different types of ending were found: (1) type I, its tonic discharge was not altered following ASt at 100 Hz for 10 s, while type II was significantly inhibited even at a frequency of 50 Hz; (2) at 300 Hz, both types of endings were inhibited, however, type I recovered in less than 4 s, while type II took more than 15 s to return to control level, and a silent period (1-5 s) was found in type II but not in type I; (3) the effective minimum inhibitory frequency for type I and type II was 200 and 50 Hz, respectively. These results suggest that type I and type II endings may correspond to the primary and the secondary endings of the muscle spindle whose sensitivity may be modulated antidromically by the dorsal root reflex.

Animals↗

Evidence for the involvement of dopamine D(1) and D(2) receptors in mediating the decrease of food intake during repeated treatment with amphetamine.

Repeated treatment with amphetamine (AMPH), a well-known anorectic agent, into animals could induce anorexia on day 1 and produce a gradual reversion of food intake (tolerant anorexia) on the following days. It is unknown whether these feeding changes are related to dopamine (DA) and/or noradrenergic neurotransmission. Thus, the present study investigated the subtype of receptor mediating AMPH-induced anorexia. Daily food intake was measured after various drugs were given. Pretreatment with haloperidol, an antagonist of DA receptors, may lead to inhibition of AMPH-induced anorexia. However, pretreatment with the alpha-adrenoceptor antagonist phentolamine, and the beta-adrenoceptor antagonist propranolol, failed to modify the action of AMPH, suggesting the involvement of DA receptors but not adrenoceptors in the action of AMPH-induced anorexia. Furthermore, pretreatment with SCH 23390 at a dose sufficient to block D(1) receptors or pimozide at a dose sufficient to inhibit D(2) receptors blocked AMPH-induced anorexia, indicating the involvement of D(1) and D(2) receptors. In a study of tolerant anorexia, repeated treatment with the D(1)/D(2) agonist apomorphine, but not the D(1) agonist SKF 38393 or D(2) agonist quinpirole, induced an AMPH-like tolerant feeding response, providing evidence for conjoint action of D(1) and D(2) receptors in the effect. The present results suggest that both D(1) and D(2) receptors are involved in anorexia and tolerant anorexia induced by chronic intermittent administration of AMPH.

Amphetamine↗